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Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia (AML-14A)

Primary Purpose

Leukemia, Myelodysplastic Syndromes

Status

Unknown status

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

clofarabine

cytarabine

idarubicin

About this trial

This is an interventional treatment trial for Leukemia focused on measuring adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with inv(16)(p13;q22), untreated adult acute myeloid leukemia, de novo myelodysplastic syndromes, secondary acute myeloid leukemia

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following by WHO criteria:
- Acute myeloid leukemia (AML) (≥ 20% bone marrow blasts by bone marrow aspiration or biopsy)
  - No acute promyelocytic leukemia (M3)
  - All cytogenetic groups allowed, except for the following:
    - t(15;17)
    - t(8;21) or inv(16) AND a WBC count at diagnosis of < 100,000/μL
  - Primary or secondary AML allowed, including AML after myelodysplasia (MDS)
- High-risk MDS (≥ 10% bone marrow blasts by bone marrow aspiration or biopsy)
No chronic myelogenous leukemia in blast crisis or AML supervening a myeloproliferative disorder
Previously untreated disease, except for ≤ 14 days of hydroxyurea
No CNS leukemia

PATIENT CHARACTERISTICS:

WHO performance status 0-2
Serum creatinine ≤ 1.0 mg/dL or glomerular filtration rate > 60 mL/min
AST/ALT ≤ 2.5 times upper limit of normal (ULN)
ALP ≤ 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for ≥ 3 months after completion of study treatment
No active uncontrolled infection
No HIV positivity
No psychological, familial, sociological, or geographical conditions precluding compliance with study treatment or follow up
No concurrent severe uncontrolled cardiovascular disease (i.e., symptomatic congestive heart failure or symptomatic ischemic heart disease [NYHA class III-IV])
No concurrent malignant disease

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No concurrent cytotoxic drugs or experimental therapies (e.g., antiangiogenic drugs, tyrosine kinase inhibitors)

Sites / Locations

A.Z. Sint-JanRecruiting
Institut Jules Bordet
CHU Sart-Tilman
University Hospital Rebro
Hôpital Saint Antoine AP-HP
Azienda Ospedallera Universitaria - Policlinico Tor VergataRecruiting
Univesita Degli Studi "La Sapienza"Recruiting
Leiden University Medical Center
Radboud University Nijmegen Medical CenterRecruiting
Jeroen Bosch ZiekenhuisRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm I

Arm II

Arm Description

Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.

Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.

Outcomes

Primary Outcome Measures

Toxicity as assessed by CTCAE v3.0 (Phase I)

Response rate (Phase II)

Secondary Outcome Measures

Toxicity as assessed by CTCAE v3.0 (Phase II)

Response rate (Phase I)

Duration of survival

Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate

Disease-free survival from CR/CRi

Incidence of relapse and incidence of death in CR/CRi

Full Information

NCT ID

NCT00838240

First Posted

February 5, 2009

Last Updated

July 19, 2012

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adulto

1. Study Identification

Unique Protocol Identification Number

NCT00838240

Brief Title

Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia

Acronym

AML-14A

Official Title

Clofarabine in Combination With a Standard Remission Induction Regimen (AraC and Idarubicin) in Patients 18-60 Years Old With Previously Untreated Intermediate and Bad Risk Acute Myelogenous Leukemia (AML) or High Risk Myelodysplasia (MDS) : a Phase I-II Study of the EORTC-LG and GIMEMA (AML-14A Trial)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Unknown status

Study Start Date

November 2008 (undefined)

Primary Completion Date

December 2012 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adulto

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as clofarabine, cytarabine, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and idarubicin in treating patients with intermediate-risk or high-risk acute myeloid leukemia or high-risk myelodysplasia.

Detailed Description

OBJECTIVES: Primary To determine the optimum dose of clofarabine in combination with cytarabine and idarubicin in patients with previously untreated intermediate- and high-risk acute myeloid leukemia or high-risk myelodysplasia. (Phase I) To determine the safety and tolerance of this regimen in order to determine the recommended phase II dose. (Phase I) To explore the antitumor activity of this regimen in these patients. (Phase II) To determine the activity expressed as complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate following induction therapy. (Phase II) Secondary To determine the activity expressed as CR/CRi rate following induction (1 or 2 courses) and consolidation therapy. (Phase I) To determine hematopoietic recovery (platelets and neutrophils) after induction and consolidation therapy. To determine safety and tolerability of this regimen. (Phase II) To determine activity expressed as CR/CRi rate after consolidation therapy. (Phase II) To determine feasibility of blood CD34 harvesting after consolidation therapy. (Phase II) To determine disease-free and overall survival from CR/CRi. (Phase II) OUTLINE: This is a multicenter, phase I, dose-escalation study of clofarabine followed by an randomized phase II study. Patients are stratified according to center, and presence of poor prognostic features (WBC at diagnosis ≥ 100,000/μL vs presence of very high risk cytogenetic features -5/5q-, -7/7q-, presence of complex abnormalities [> 3 abnormalities], 3q, t[6;9], or t[9;22]). Patients are randomized to 1 of 2 treatment arms. Induction therapy: Arm I: Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10. Arm II: Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10. Consolidation therapy: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-6 and idarubicin IV over 5 minutes once daily on days 4-6. After completion of study therapy, patients are followed periodically for 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Myelodysplastic Syndromes

Keywords

adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with inv(16)(p13;q22), untreated adult acute myeloid leukemia, de novo myelodysplastic syndromes, secondary acute myeloid leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

114 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Experimental

Arm Description

Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.

Arm Title

Arm II

Arm Type

Experimental

Arm Description

Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.

Intervention Type

Drug

Intervention Name(s)

clofarabine

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

cytarabine

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

idarubicin

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Toxicity as assessed by CTCAE v3.0 (Phase I)

Title

Response rate (Phase II)

Secondary Outcome Measure Information:

Title

Toxicity as assessed by CTCAE v3.0 (Phase II)

Title

Response rate (Phase I)

Title

Duration of survival

Title

Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate

Title

Disease-free survival from CR/CRi

Title

Incidence of relapse and incidence of death in CR/CRi

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following by WHO criteria: Acute myeloid leukemia (AML) (≥ 20% bone marrow blasts by bone marrow aspiration or biopsy) No acute promyelocytic leukemia (M3) All cytogenetic groups allowed, except for the following: t(15;17) t(8;21) or inv(16) AND a WBC count at diagnosis of < 100,000/μL Primary or secondary AML allowed, including AML after myelodysplasia (MDS) High-risk MDS (≥ 10% bone marrow blasts by bone marrow aspiration or biopsy) No chronic myelogenous leukemia in blast crisis or AML supervening a myeloproliferative disorder Previously untreated disease, except for ≤ 14 days of hydroxyurea No CNS leukemia PATIENT CHARACTERISTICS: WHO performance status 0-2 Serum creatinine ≤ 1.0 mg/dL or glomerular filtration rate > 60 mL/min AST/ALT ≤ 2.5 times upper limit of normal (ULN) ALP ≤ 2.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for ≥ 3 months after completion of study treatment No active uncontrolled infection No HIV positivity No psychological, familial, sociological, or geographical conditions precluding compliance with study treatment or follow up No concurrent severe uncontrolled cardiovascular disease (i.e., symptomatic congestive heart failure or symptomatic ischemic heart disease [NYHA class III-IV]) No concurrent malignant disease PRIOR CONCURRENT THERAPY: See Disease Characteristics No concurrent cytotoxic drugs or experimental therapies (e.g., antiangiogenic drugs, tyrosine kinase inhibitors)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Hilde Breyssens

hilde.breyssens@eortc.be

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roel Willemze

Organizational Affiliation

EORTC (Phase I) - Leiden University Medical Center, NL

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Dominik Selleslag

Organizational Affiliation

EORTC (Phase II) - AZ Sint-Jan, BE

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Giovanna Meloni

Organizational Affiliation

GIMEMA (Phase I & II) - Universita Degli Studi "La Sapienza", IT

Official's Role

Principal Investigator

Facility Information:

Facility Name

A.Z. Sint-Jan

City

Brugge

Country

Belgium

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dominik Selleslag

Facility Name

Institut Jules Bordet

City

Brussel

Country

Belgium

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dominique Bron

Facility Name

CHU Sart-Tilman

City

Liège

Country

Belgium

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Frédéric Baron

Facility Name

University Hospital Rebro

City

Zagreb

Country

Croatia

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Boris Labar

Facility Name

Hôpital Saint Antoine AP-HP

City

Paris

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Olivier Legrand

Facility Name

Azienda Ospedallera Universitaria - Policlinico Tor Vergata

City

Roma

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sergio Amadori

Facility Name

Univesita Degli Studi "La Sapienza"

City

Roma

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Giovanna Meloni

Facility Name

Leiden University Medical Center

City

Leiden

Country

Netherlands

Individual Site Status

Active, not recruiting

Facility Name

Radboud University Nijmegen Medical Center

City

Nijmegen

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Petra Muus

Facility Name

Jeroen Bosch Ziekenhuis

City

s' Hertogenbosch

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hans Pruijt

12. IPD Sharing Statement

Learn more about this trial

Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia

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